Few funding sources exist for the crucial, early stage experiments needed to demonstrate to national funding agencies that such new approaches are viable and rewarding. Early stage development funding for new innovations with commercial potential is scarce as well. The BIO5 Seed Grant Program for interdisciplinary research projects helps fill this gap.
The desired outcome from the BIO5-funded projects is that they become competitive in applications for multidisciplinary, multi-investigator grants from the National Institutes of Health, National Science Foundation, and other national funding agencies and/or further the number of translational development of potentially commercial projects.
The awards are based on quality of science, expertise of investigators, potential for success, interdisciplinary nature and potential for competing favorably for federal funding.
Eight of the 33 seed grant applications in 2006 were selected for funding based on both external and internal peer review:
Funded Projects and Research Teams
Engineered MHC Class I Molecules as Novel Vaccines against Influenza
PI: Samita Andreansky, Ph.D, Pediatrics
Co-PI: Lonnie Lybarger, Ph.D., BIO5, Cell Biology & Anatomy and Microbiology & Immunology
This project explores the use of DNA vaccines that target immune responses to regions of the virus that are highly conserved, which means they are not prone to mutation. These studies will employ a novel engineering method to create genetic constructs that will efficiently present a high level of conserved antigens to the immune system The goal is to facilitate vaccines that can generate protective response and reduce viral transmission. These novel vaccines are intended to offer partial protection as a first line of defense during a pandemic, to be followed by strain-matched vaccines when available.
Modeling Partially Understood Biological Networks
PI: Parker Antin, Ph.D., BIO5, and Cell Biology and Anatomy
Co-PI: Leo Lopes, Ph.D, Systems and Industrial Engineering
Virtually all biological processes involve complex network interactions among groups of molecules, many of which are either unknown or have unknown functions. The purpose of this research is to develop mathematical formulas to infer the likely design of some of those network interactions in which some molecules are unknown or uncharacterized, and to apply these formulas to a process that is important for normal embryo development and the manifestation of certain diseases. This work also has broad implications in engineering and defense, where portions of non-biological networks are frequently missing.
Continuum Protein Models Applied to the Design of Diagnostic and Therapeutic Reagents for Type 2 Diabetes
PI: Alain Goriely, Ph.D., BIO5, Department of Mathematics
Co-PIs: Andrew Hausrath, Ph.D., Biochemistry and Molecular Physics
Tsu-Shuen Tsao, Ph.D., Biochemistry
Diabetes is a major health threat in the United States and current anti-diabetic therapies are problematic and can have side effects such as weight gain. Adiponectin is a hormone secreted from fat tissue that may circumvent some of these problems because it enhances insulin's ability to lower glucose levels and it stimulates fat burning. Diabetic patients have decreased circulating levels of adiponectin.
Elucidating the mechanisms by which adiponectin functions is complicated by the fact that it exists in the bloodstream as three distinct forms. The largest adiponectin isoform is extremely stable in circulation, making it an ideal candidate for a new drug that does not require frequent injections. This project will combine novel mathematical modeling and traditional biochemical approaches to trap the adiponectin molecule in this active form, which could lead to a novel therapeutic approach for type II diabetes.
The Application of Stem Cells to Joint Reconstruction
PI: David T. Harris, Ph.D.; BIO5 and Dept. Microbiology and Immunology
Co-PI: John A. Szivek, Ph.D.; BIO5 and Orthopaedic Surgery and Biomedical Engineering
Joint pain and loss of mobility represents the most common cause of impairment in the United States. Nearly 50 percent of Americans ages 25 to 74 years report having had knee pain and more patients undergo surgery to place orthopaedic implants than any other type of implant. Although numerous procedures have been developed for the treatment of damaged joint cartilage, currently none consistently restore the long-term function. The purpose of this project is to compare cultured cartilage cells with stem cells from cord blood (from donated samples), adipose (from liposuction samples) and mesenchymal (from bone marrow), and evaluate their potential for joint reconstruction/cartilage generation.
Integrated Capture and Spectroscopic Detection of Viruses
PI: Mark Riley, Ph.D., BIO5, Department of Agricultural & Biosystems Engineering
Co-PIs: Kelly A. Reynolds, MSPH, Ph.D., Community Environment and Policy, College of Public Health
Pierre Lucas, Ph.D., Materials Science and Engineering
The presence of viruses in drinking water is a continual concern for municipalities and leads to thousands of cases of individual disease each year. This project combines the expertise of an environmental microbiologist, material scientist, and biological engineer to detect, quantify, and identify viruses in water systems. This team will develop a novel approach to capture viruses from water (for drinking or other domestic use) based on the electrical charge that is naturally present on viruses at neutral pH. The viruses will be targeted to a glassy material which can be probed using infrared (IR) spectroscopy. IR can discriminate between different types of viruses and from bacteria and other non-biological materials. The approach has the potential to quantify low levels of viruses and to be used in line with current water purification and sampling systems.
Cutting through the Mechanochemical Pathway of DNA Endonculeases
PI: Koen Visscher, Ph.D., BIO5, Physics, and Molecular & Cellular Biology
Co-PI: Nancy Horton, Ph.D., Biochemistry & Molecular Biophysics
DNA endonucleases are enzymes that cut DNA at very specific and well-defined locations, and for this reason, they are widely used in modern-day molecular biology and biotechnology. They may one day be applied to cut out the specific genes needed for gene therapy. Despite wide use, many questions remain about how these enzymes work. Manipulation of single DNA molecules could result in unprecedented and novel insight into the molecular mechanism of these enzymes that work like molecular scissors. The long-term goal is to unravel the mechanochemical the coupled biochemical and mechanical pathways of these enzyme-DNA interaction.
Development of Novel Blockers of Aquaporin-4 Channels with Translational Relevance to Stroke Induced Brain Edema
PI: Andrea Yool, Ph.D., BIO5, Physiology and Pharmacology
Co-PI: Gary Flynn, Ph.D., BIO5 and Pharmacology & Toxicology
Gerald Maggiora, Ph.D., BIO5 and Pharmacology & Toxicology
Aquaporins (AQP4) are protein molecules that enable the normal maintenance of fluid balance in the brain, but under severe conditions such as ischemic stroke, may also enhance pathological swelling (edema). Extensive brain edema is a major cause of death in patients with large strokes; unfortunately, ideal strategies for management of brain edema remain elusive. In prior work, mice that were genetically modified to eliminate AQP4 showed reduced edema and a better neurologic outcome after stroke, suggesting a blocker of AQP4 might be of significant medical value. This research team has discovered a lead compound as the first known blocker for AQP4. The goal of the ongoing project is to synthesize and optimize this AQP4 blocker.
Novel Applications of Nanotechnology: Microdevices to Capture Circulating Tumor Cells
PI: Yitshak Zohar, Ph.D., BIO5, Aerospace and Mechanical Engineering
Co-PIs: Ronald L. Heimark, Ph.D., Surgery and Physiology
Roberto Z. Guzman, Ph.D., Chemical and Environmental Engineering
James C. Baygents, Ph.D., Chemical and Environmental Engineering
Circulating prostate or breast cancer cells have unique adhesion molecules (cadherins) on the cell membranes. This research team is fabricating microdevices that can selectively extract circulating metastatic tumor cells from the blood of cancer patients by taking advantage of this particular type of adhesion. They have developed a process to test the feasibility of using such microdevices to capture the target cells.